Laser preconditioning with a 755-nm picosecond diffractive lens array accelerates cutaneous wound healing via early activation of reparative gene networks

Preconditioning the skin with non-ablative laser energy represents a promising strategy to enhance tissue repair, yet its biological mechanisms remain incompletely defined. This study investigated whether pre-injury stimulation using a 755-nm picosecond Alexandrite laser (PSAL) equipped with a diffractive lens array (DLA) could accelerate wound healing and modulate molecular pathways in vivo. Full-thickness dorsal excisional wounds were created in Sprague–Dawley rats and assigned to three groups: laser pre-treated, post-treated, and untreated controls. Wound closure was monitored for 14 days, and the expression of wound-healing–related genes ( Ctgf , bFgf , Col I , Col III , Tgf-β1/2/3 , and Mmp9 ) was quantified by real-time PCR. The pre-treated group exhibited significantly faster wound closure (46.9% closure vs. 12.5% in controls, p = 0.0038) and earlier upregulation of matrix-remodeling genes during wound repair. Tgf-β1 and Tgf-β2 levels increased 5–16 fold within 4 days, while Mmp9 mRNA expression peaked 11-fold above controls at day 14, suggesting enhanced extracellular matrix remodeling and tissue maturation. Furthermore, western blot analysis demonstrated that pre-treatment significantly increased Col I and MMP9 protein expression at day 1, before the post-treatment group received laser exposure. Collectively, these findings suggest that laser preconditioning primes the skin for regeneration in association with early activation of reparative gene networks before injury. This non-invasive approach provides a biologically supported preclinical rationale for a clinically translatable strategy to optimize postoperative wound healing and potentially reduce scar formation risk.